PROJECT SUMMARY/ ABSTRACT An unprecedented public health emergency due to the COVID-19 pandemic is unfolding worldwide and the United States has been the epicenter of the pandemic since March 26, 2020. No prior global pandemic of this scale has overlapped temporally with the HIV pandemic. Despite this, given the breathtaking speed at which the pandemic has progressed, very little is known about the interplay between HIV and SARS-CoV-2 given that COVID-19 has only recently entered areas of high HIV prevalence. The COVID-19 pandemic is threatening worldwide gains in UNAIDS 90:90:90 targets for HIV by disrupting health systems, economies, and the health of people with HIV. San Francisco was the first city in the U.S. to impose ?shelter in place? public health measures on March 16, 2020. Given the need to limit in-person visits to counter the spread of COVID-19, research on the impact on HIV outcomes, retention in care, and sociobehavioral outcomes will be crucial to develop interventions to attenuate COVID-19's deleterious impact and to plan for future pandemics. Whether people with HIV (PWH) are more or less susceptible to COVID-19 or severe disease is unknown; some of the risk factors for severe COVID-19 (older age, cardiovascular disease, pulmonary disease) are more prevalent among PWH but HIV medications such as tenofovir and its metabolites could be protective. PWH in low-income settings have marginal housing and food insecurity, increasing transmission risk. Given the impact of HIV on immune responses, it is also important to understand if PWH will have less durable immunity against COVID-19 following infection. Finally, the impact of the COVID-19's disruption of medical and social services for PWH needs urgent study, both during the crisis and in its aftermath, since COVID-19 has the potential to eradicate the progress made on Ending the HIV Epidemic to date. This proposal will answer three vital questions concerning the interplay between the two viruses. The site of the study will be at the Ward 86 HIV Clinic, a large safety-net clinic for publicly-insured patients with HIV in San Francisco, near the neighborhoods experiencing concentrated COVID-19 epidemics. Aim 1 will provide novel, urgently needed insights into how SARS-CoV-2 infection risk, prevalence and clinical outcomes vary by HIV status and/or antiretroviral regimen (i.e. tenofovir). Aim 2 will explore whether HIV infection will impair humoral or T-cell responses to COVID-19, providing insights for therapeutic and vaccine development. Aim 3 data will evaluate the impact of disruption of healthcare and social support systems on PWH, including viral suppression; retention in care; hospitalizations, co-morbidity outcomes, and non-COVID-19 related death; healthcare utilization during COVID019; and socio-behavioral outcomes during and after social distancing to assess isolation, food insecurity, stress, substance use, stigma, and resilience. Harnessing, the research infrastructure of the UCFAR, citywide COVID-19 registries, and a large, aging population of PWH served by the Ward 86 clinic, this grant will put immediate, high-impact studies in place to track the colliding pandemics.